This project consists of a longitudinal, prospective study of the population-at-risk for osteoporosis. Research subjects are 191 normal women who were aged 35-45 at the start of the study in 1967. Observations have been made once every five years consisting of demographic, anthropometric, calcium kinetic, calcium metabolic, hormonal, and physiological measurements, as well as radiogrammetric and photon-densitometer measurement of bone mass. The purposes of the project are: (1) to obtain comprehensive longitudinal data on various measures of calcium and bone metabolism and related physiological functions in a group of untreated women from the perimenopausal period to the time of osteoporotic symptoms; (2) to provide an exhaustive physiological profile both on women who subsequently develop symptomatic osteoporosis and on those who do not, thereby allowing prospective characterization of the differences between them and of the factors influencing those differences; (3) to permit better identification of the osteoporosis-prone subset and thereby to provide both a rational basis for prophylactic treatment and the identification of subjects who should be its target; (4) to characterize cross-sectional inter-relationships between major physiologic variables during this key era of osteoporosis development; and finally (5) to provide a comprehensive database for testing hypotheses about associations among variables developed by the applicants and others outside the context of this proposal. The plan for this next grant period is to: (1) maintain surveillance of this cohort until a sufficient number of osteoporosis-related fractures develop, and (2) to continue obtaining major outcome measures (e.g. bone mass, fractures) every three years. At the onset of the new project period the study population will be in the age-range 63-72. Forty-seven probably fragility-related fractures have occurred in the cohort to date.